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Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
2013 (English)In: Bioprocess and biosystems engineering (Print), ISSN 1615-7591, E-ISSN 1615-7605, Vol. 36, no 10, 1375-1384 p.Article in journal (Refereed) Published
Abstract [en]

A soft sensor approach is described for controlling metabolic overflow from mixed-acid fermentation and glucose overflow metabolism in a fed-batch cultivation for production of recombinant green fluorescence protein (GFP) in Escherichia coli. The hardware part of the sensor consisted of a near-infrared in situ probe that monitored the E. coli biomass and an HPLC analyzer equipped with a filtration unit that measured the overflow metabolites. The computational part of the soft sensor used basic kinetic equations and summations for estimation of specific rates and total metabolite concentrations. Two control strategies for media feeding of the fed-batch cultivation were evaluated: (1) controlling the specific rates of overflow metabolism and mixed-acid fermentation metabolites at a fixed pre-set target values, and (2) controlling the concentration of the sum of these metabolites at a set level. The results indicate that the latter strategy was more efficient for maintaining a high titer and low variability of the produced recombinant GFP protein.

Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2013. Vol. 36, no 10, 1375-1384 p.
Keyword [en]
Soft sensors, Software sensors, Bioprocess monitoring and control, Fed-batch cultivation control, Overflow metabolism, Mixed-acid fermentation
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-98661DOI: 10.1007/s00449-012-0840-zISI: 000324214400005OAI: diva2:655273

Funding Agencies|Linkoping University||

Available from: 2013-10-10 Created: 2013-10-10 Last updated: 2013-10-17Bibliographically approved

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Gustavsson, RobertMandenius, Carl-Fredrik
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